The vision of the Center for Human Health and the Environment (CHHE) is to become a global leader in environmental health sciences (EHS) along the continuum from genes to populations by building on NC State?s unique research strengths and resources in quantitative biology, -omics and analytical technologies, and diverse model organisms, as well as its emerging strength in human population science. Through the purposeful interfacing of different disciplines and a systems biology framework integrating all levels of biological organization - biomolecule, pathway, cell, tissue, organ, model organism, human, and human population - CHHE will elucidate fundamental mechanisms through which environmental stressors interface with pathways, the genome, and epigenome to influence human health outcomes. CHHE has made outstanding progress in the first funding cycle. CHHE has significantly: (1) advanced innovative multi- disciplinary EHS team research; (2) expanded its NIEHS grant base; (3) increased EHS capacity at its partner institutions, East Carolina University and North Carolina Central University; (4) cultivated the next generation of EHS leaders; and (5) developed multi-directional engagement with communities affected by exposure to toxic metals and per- and polyfluoroalkyl substances. During our first funding cycle, four Research Interest Groups (RIGs) evolved organically and the Emerging Contaminants, Environmental Epigenetics and Genetics, Pulmonary Health, and Behavior and Neuroscience RIGs now represent CHHE thematic areas. In the coming cycle, we have enhanced our three facility cores to increase the impact and the basic science and translational capacity of our membership. The Systems Technologies Core provides cutting-edge technologies involving genomics, metabolomics, metallomics, and proteomics. The Comparative Pathology Core provides pathologic phenotypic assessment of the many model organisms used by members and imaging support with links back to omics technologies. The Integrative Health Science Facility Core facilitates bidirectional translation between basic science and public health outcomes by providing data science analysis and visualization support for analysis of human population and multi-omic studies as well as population-based study expertise. As a land- grant university, NC State has a dedicated community engagement philosophy that augments CHHE?s Community Engagement Core and fosters relationships between CHHE and affected communities in NC which leads to collaborative interaction among researchers, educators, and citizens to enhance EHS knowledge, literacy, and health. A strong Career Development Program for early- and mid-career investigators is coordinated with a robust Pilot Project Program that supports collaborative and multidisciplinary EHS projects to enhance the research success of our members. Our CHHE mission is to continue to evolve as a premier NIEHS EHS Core Center and serve as the nexus of EHS research at NC State by providing focus, resources, and leadership for interdisciplinary research that will improve human health locally, nationally, and globally.